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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-10278

Zeilhofer, H U; Brune, K (2006). Antipyretic analgesics: basic aspects. In: McMahon, S B; Koltzenburg, M. Wall and Melzack's Textbook of Pain. Edinburgh: Elsevier, 459-469.

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Antipyretic analgesics are among the most often used medications worldwide. Their major mechanism of action is the blockade of synthesis of prostanoids. These are lipid mediators, which are produced from arachidonic acid in response to tissue damage and inflammation. Constitutive cyclooxygenase (COX) 1 and inducible COX-2 produce the
prostaglandin precursors prostaglandin G2 and prostaglandin H2 from arachidonic acid. These precursors are subsequently converted into the different biologically active prostaglandins and thromboxane. Among these, prostaglandin E2 is probably the most important one for pain sensitization. It facilitates nociception not only in the peripheral inflamed tissue but also at central sites, namely the spinal cord dorsal horn. Antipyretic analgesic should therefore no longer be considered as ‘(solely) peripherally acting analgesics’. They are classified according to their physiochemical properties, clinical actions, and pharmacodynamic selectivity. Acidic antipyretic analgesics (NSAIDs) are potent and efficient inhibitors of the two cyclooxygenases, and exert, in addition to their analgesic and antipyretic effect, a profound anti-inflammatory action. Most of their unwanted effects including their gastrointestinal toxicity are also due to inhibition of prostaglandin synthesis. Classical non-acidic antipyretic analgesics—for example, paracetamol (acetaminophen)— are relatively poor inhibitors of cyclooxygenases. They are analgesic and antipyretic, but lack significant anti-inflammatory properties. Because the inducible cyclooxygenase isoform COX-2 produces most of the prostaglandins triggering inflammation and nociceptive sensitization, selective COX-2 inhibitors have been developed as analgesics and anti-inflammatory drugs. Like classical NSAIDs these ‘coxibs’ are antipyretic, analgesic and anti-inflammatory, but show significantly reduced gastrointestinal toxicity compared to classical NSAIDs.
As we learn more about the molecular mechanisms of the pronociceptive action of prostaglandins new therapeutic strategies may arise at the horizon. Future developments may include inhibitors of specific prostaglandin synthases and of prostaglandin receptor antagonists.



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Item Type:Book Section, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Pharmacology and Toxicology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Deposited On:27 Mar 2009 13:06
Last Modified:05 Apr 2016 12:49
Official URL:http://www.elsevier.com/wps/find/bookdescription.cws_home/705708/description#description
Related URLs:https://biblio.unizh.ch/F/?local_base=UZH01&con_lng=GER&func=find-b&find_code=SYS&request=001524682

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